Gastroenterology - Haemochromatosis, Wilson's Disease, Alpha 1 Antitrypsin deficiency

Question 1

Haemochromatosis - what is it?

Answer 1

It is a autosomal recessive disorder of iron absorption and metabolism, resulting in iron accumulation

Question 2

Haemochromatosis - what is it caused by?

Answer 2

Caused by inheritance of mutations in the HFE gene located on both copies of chromosome 6

Question 3

Haemochromatosis - what are the symptoms?

Answer 3

Early disease - asymptomatic

Presenting symptoms:

1. Arthralgia
2. Chronic fatigue
3. Erectile dysfunction - Fe deposits in gonads
4. Pigmentation - bronze/slate-grey
5. DM - Fe in pancreas
6. Liver cirrhosis - hepatocellular deposition
7. Hair loss
8. Cognitive - memory and mood disturbances
9. Cardiomyopathy
10. Chondrocalcinosis - calcium deposits in joints, causing arthritis

Question 4

Haemochromatosis - what investigations can you do?

Answer 4

Genetic testing for C282Y and H63D mutations

Liver biopsy with PERLs STAIN

Iron study profile

MRI - to see Fe deposits in liver and heart

Question 5

Haemochromatosis - what would you see on a positive iron study profile?

Answer 5

Raised ferritin (500ug/L) and iron
Transferrin saturation >55% in men, >50% in women

Question 6

Haemochromatosis - management?

Answer 6

1ST LINE - Venesection, weekly blood removal

2ND LINE - Desferrioxamine

Manage and treat complications

Genetic counselling

Question 7

Wilson’s Disease - what is it?

Answer 7

Autosomal recessive disorder characterised by excessive copper deposits in body tissues

Question 8

Wilson’s Disease - what abnormalities does the disease cause in the body?

Answer 8

Increased small intestine copper absorption

Decreased hepatic excretion of copper

Question 9

Wilson’s Disease - where is the defect found on the chromosome?

Answer 9

Defect is found on ATP7B on chromosome 13

Question 10

Wilson’s Disease - what are the 3 main presenting systems and their features?

Answer 10

Present with 1 or more of 3 system presentations:

LIVER:
1. Chronic hepatitis -> liver cirrhosis

NEUROLOGICAL:

1. Concentration disturbance
2. Dysarthria
3. Dystonia
4. Cu depo in Basal Ganglia -> parkinsonism (triad of parkinsons, symmetrical symptoms)

PSYCHIATRIC:

1. Mild depression
2. Psychosis

Question 11

Wilson’s Disease - what are some signs?

Answer 11

Kayser-Fleischer Rings - deposits of Cu in the descemet membrane of cornea

Slit Lamp examination

Question 12

Wilson’s Disease - what are other features?

Answer 12

Haemolytic anaemia

Renal tubular damage

Osteopenia

Question 13

Wilson’s Disease - diagnosis?

Answer 13

SERUM CAERULOPLASMIN, protein that carries Cu in blood (not specific as can be raised in cancer or inflammation)

Liver biopsy - test for CU content, GOLD STANDARD

24 hour urine Cu assay

Serum Cu -> decreased

Check for Kayser-Fleischer Rings with Slit Lamp

Question 14

Wilson’s Disease - management

Answer 14

Remove excessive copper from body -> copper chelation:
Penicillamine 1ST LINE

Trientene

Question 15

Alpha 1 Antitrypsin Deficiency (A1AT) - what is it?

Answer 15

Inherited condition where the PROTEASE INHIBITOR (Pi) alpha 1 antitrypsin is not produced enough by the liver due to a genetic abnormality

Question 16

Alpha 1 Antitrypsin Deficiency - what is alpha 1 antitrypsin and elastase?

Answer 16

It is a protease inhibitor

Elastase is an enzyme secreted by neutrophils that digests connective tissue

Alpha 1 antitrypsin is produced by liver, travels around body and protects cells by inhibiting the NEUTROPHIL ELASTASE enzyme

Question 17

Alpha 1 Antitrypsin Deficiency - what chromosome is it coded for on?

Answer 17

Chromosome 14

Question 18

Alpha 1 Antitrypsin Deficiency - what type of genetic inheritance is it?

Answer 18

Autosomal Recessive

Question 19

Alpha 1 Antitrypsin Deficiency - what are the two main organs affected and associated diseases?

Answer 19

Liver - Liver cirrhosis

Lungs - Bronchiectasis and emphysema in lungs

Question 20

Alpha 1 Antitrypsin Deficiency - how does the genetic defect lead to liver cirrhosis?

Answer 20

Alpha 1 antitrypsin made in liver

In AIAD, abnormal version made

Abnormal version gets trapped in liver, builds up, causes liver damage

Damage progresses to cirrhosis

Can lead to hepatocellular carcinoma

Question 21

Alpha 1 Antitrypsin Deficiency - how does the genetic defect lead to lung problems?

Answer 21

Lack of normal alpha 1 antitrypsin means there is excess of protease enzymes that attack and digest connective tissue in lungs

Leads to emphysema and bronchiectasis over time

Question 22

Alpha 1 Antitrypsin Deficiency - what investigations can you do?

Answer 22

1. AIAT concentrations - LOW
2. LIVER BIOPSY - cirrhosis, and acid-Schiff-positive staining globules (stain highlights abnormal A1AT proteins) in hepatocytes
3. Genetic screening
4. CT thorax for emphysema and bronchiectasis

Question 23

Alpha 1 Antitrypsin Deficiency - management?

Answer 23

1. Symptomatic managment
2. No smoking
3. IV AIAT protein concentrates
4. Surgery - organ transplant